Effectiveness of Hypertonic Dextrose Injection (Prolotherapy) in Plantar Fasciopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically review the effectiveness of hypertonic dextrose prolotherapy (DPT) in plantar fasciopathy (PF) compared with other non-surgical treatments. DATA SOURCES: PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Allied and Complementary Medicine Database, Global Health, Ovid Nursing Database, Dimensions, and WHO ICTRP were searched from inception to April 30th, 2022. STUDY SELECTION: Two independent reviewers selected randomized controlled trials (RCTs) that evaluated the effectiveness of DPT in PF compared with non-surgical treatments. Outcomes included pain intensity, foot and ankle function, and plantar fascia thickness. DATA EXTRACTION: Two independent reviewers conducted data extraction. Risk of bias (RoB) assessment was conducted using the Cochrane Risk of Bias 2 (RoB 2) tool, and certainty of evidence was assessed with Grading of Recommendation Assessment, Development, and Evaluation (GRADE). DATA SYNTHESIS: Eight RCTs (n=469) met the inclusion criteria. Pooled results favored the use of DPT versus normal saline (NS) injections in reducing pain (weighted mean difference [WMD] -41.72; 95% confidence interval [CI] -62.36 to -21.08; P<.01; low certainty evidence) and improving function [WMD -39.04; 95% CI -55.24 to -22.85; P<.01; low certainty evidence] in the medium term. Pooled results also showed corticosteroid (CS) injections was superior to DPT in reducing pain in the short term [standardized mean difference 0.77; 95% CI 0.40 to 1.14; P<.01; moderate certainty evidence]. Overall RoB varied from "some concerns" to "high". The overall certainty of evidence presented ranges from very low to moderate based on the assessment with the GRADE approach. CONCLUSION: Low certainty evidence demonstrated that DPT was superior to NS injections in reducing pain and improving function in the medium term, but moderate certainty evidence showed that it was inferior to CS in reducing pain in the short term. Further high-quality RCTs with standard protocol, longer-term follow-up, and adequate sample size are needed to confirm its role in clinical practice.

Metformin use and the risk of total knee replacement among diabetic patients: a propensity-score-matched retrospective cohort study.

Metformin has been shown to modulate meta-inflammation, an important pathogenesis in knee osteoarthritis (OA). The study aimed to test the association between regular metformin use with total knee replacement (TKR) in patients with diabetes. This is a retrospective study with electronic records retrieved in Hong Kong public primary care. Patients with diabetes aged ≥ 45 who visited during 2007 to 2010, were followed up for a four-year period from 2011 to 2014 to determine the incidence of TKR. Propensity score matching based on age, sex, co-medications and chronic conditions was conducted to adjust for confounding. Cox regression was implemented to examine the association between metformin use and TKR. In total, 196,930 patients were eligible and 93,330 regular metformin users (defined as ≥ 4 prescriptions over the previous year) and non-users were matched. Among 46,665 regular users, 184 TKRs were conducted, 17.1% fewer than that among non-users. Cox regression showed that regular metformin users had a 19%-lower hazard of TKR [hazard ratio (HR) = 0.81, 95% confidence interval: 0.67 to 0.98, P = 0.033], with a dose-response relationship. Findings suggest a potential protective effect of metformin on knee OA progression and later TKR incidence among diabetic patients.

Treatment with stimulants and the risk of COVID-19 complications in adults with ADHD.

Adults with attention deficit hyperactivity disorder (ADHD) have shown higher infection rates and worse outcomes from COVID-19. Stimulant medications are prescribed as the first-line treatment for ADHD in adults and mitigate risk of negative ADHD-related health outcomes, but little is known about the association between stimulant medications and COVID-19 outcomes. The objective of this study was to assess the risks of severe COVID-19 outcomes among people with ADHD who were prescribed stimulant medications versus those who were not. This retrospective cohort study used electronic health records in the TriNetX research database. We assessed records of adults with ADHD diagnosed with COVID-19 between January 1, 2020 and June 30, 2021. The stimulant cohort consisted of 28,011 people with at least one stimulant prescription; the unmedicated cohort comprised 42,258 people without prescribed stimulants within 12 months prior to their COVID infection. Multiple logistic regression modeling was utilized to assess the presence of critical care services or death within 30 days after the onset of COVID diagnoses, controlling for patient demographics, and comorbid medical and mental health conditions. The stimulant cohort was less likely to utilize emergency department, hospital, and intensive care services than the unmedicated cohort, and had significantly lower 30-day mortality. Further research, including prospective studies, is needed to confirm and refine these findings.

Language Matters: It Is Time We Change How We Talk About Addiction and its Treatment.

The way we communicate about addiction, its treatment, and treatment outcomes matters to individuals affected by addiction, their families, and communities. Stigmatizing language can worsen addiction-related stigma and outcomes. Although non-professional terminology may be used by individuals with addiction, the role of clinicians, educators, researchers, policymakers, and community and cultural leaders is to actively work toward destigmatization of addiction and its treatment, in part through the use of non-stigmatizing language. Role-modeling better approaches can help us move away from the inaccurate, outdated view of addiction as a character flaw or moral failing deserving of punishment, and toward that of a chronic disease requiring long-term treatment. Non-stigmatizing, non-judgmental, medically-based terminology and the adoption of person-first language can facilitate improved communication as well as patient access to and engagement with addiction care. Person-first language, which shifts away from defining a person through the lens of disease (eg, the term "a person with addiction" is recommended over the terms "addict" or "addicted patient"), implicitly acknowledges that a patient's life extends beyond a given disease. While such linguistic changes may seem subtle, they communicate that addiction, chronic pain and other diseases are only one aspect of a person's health and quality of life, and can promote therapeutic relationships, reduce stigma and health and disparities in addiction care. This article provides examples of stigmatizing terms to be avoided and recommended replacements to facilitate the dialogue about addiction in a more intentional, therapeutic manner.

Dextrose Prolotherapy: A Narrative Review of Basic Science, Clinical Research, and Best Treatment Recommendations.

Prolotherapy involves the injection of nonbiologic solutions, typically at soft tissue attachments and within joint spaces, to reduce pain and improve function in painful musculoskeletal conditions. A variety of solutions have been used; dextrose prolotherapy is the most rigorously studied and is the focus of this review. Although the mechanism of action is not clearly known, it is likely to be multifactorial. Data on effectiveness for temporomandibular dysfunction are promising but insufficient for recommendations. Research on the mechanism of action and clinical effects of dextrose prolotherapy are under way.

Effectiveness of nasal irrigation for chronic rhinosinusitis and fatigue in patients with Gulf War illness: protocol for a randomized controlled trial.

INTRODUCTION: Gulf War Illness (GWI) affects 1 in 7 returned Persian Gulf War veterans. Quality-of-life impact is large; there is no cure. Chronic sinus symptoms and fatigue are common. Nasal irrigation with saline (NI-S) or xylitol (NI-X) improve sinus symptoms and fatigue in the general population. This trial will assess the effect of NI-S and NI-X on sinus and fatigue symptoms, economic outcomes and pro-inflammatory milieu among participants with GWI. METHODS: 75 participants (age 35 to 65 years, 25 in each of three arms) with GWI will be recruited from the Veteran's Administration and the community. They will use routine care for sinus symptoms and fatigue and be randomized to continued usual care alone or additional therapy with NI-S or NI-X. Participants will be able to adjust specific elements of the NI procedure. The primary outcome (Sinonasal Outcome Test, SNOT-20) and other self-reported assessments will occur at baseline, 8 and 26 weeks; lab assessment of pro-inflammatory cellular and cytokine profiles will occur at baseline and 26 weeks. Other outcomes will include fatigue-specific and overall health-related quality of life, pro-inflammatory cellular and cytokine profiles, cost-effectiveness and participant satisfaction. RESULTS: Baseline demographic and clinical data from the first 10 participants show effective participant recruitment, enrollment, randomization, retention and data collection. CONCLUSION: Early study conduct suggests that our participant-oriented approach will yield high rates of participant adherence and data capture, facilitating robust analysis. Results of this study will clarify the value of NI for chronic sinus symptoms and fatigue among patients with GWI. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01700725.

Relationships between biomechanics, tendon pathology, and function in individuals with lateral epicondylosis.

STUDY DESIGN: Single-cohort descriptive and correlational study. OBJECTIVES: To investigate the relationships between tendon pathology, biomechanical measures, and self-reported pain and function in individuals with chronic lateral epicondylosis. BACKGROUND: Lateral epicondylosis has a multifactorial etiology and its pathophysiology is not well understood. Consequently, treatment remains challenging, and lateral epicondylosis is prone to recurrence. While tendon pathology, pain system changes, and motor impairments due to lateral epicondylosis are considered related, their relationships have not been thoroughly investigated. METHODS: Twenty-six participants with either unilateral (n = 11) or bilateral (n = 15) chronic lateral epicondylosis participated in this study. Biomechanical measures (grip strength, rate of force development, and electromechanical delay) and measures of tendon pathology (magnetic resonance imaging and ultrasound) and self-reported pain and function (Patient-Rated Tennis Elbow Evaluation) were performed. Partial Spearman correlations, adjusting for covariates (age, gender, weight, and height), were used to evaluate the relationship between self-reported pain, function, and biomechanical and tendon pathology measures. RESULTS: Statistically significant correlations between biomechanical measures and the Patient-Rated Tennis Elbow Evaluation ranged in magnitude from 0.44 to 0.68 (P<.05); however, no significant correlation was observed between tendon pathology (magnetic resonance imaging and ultrasound) measures and the Patient-Rated Tennis Elbow Evaluation (r = -0.02 to 0.31, P>.05). Rate of force development had a stronger correlation (r = 0.54-0.68, P<.05) with self-reported function score than with grip strength (r = 0.35-0.47, P<.05) or electromechanical delay (r = 0.5, P<.05). CONCLUSION: Biomechanical measures (pain-free grip strength, rate of force development, electromechanical delay) have the potential to be used as outcome measures to monitor progress in lateral epicondylosis. In comparison, the imaging measures (magnetic resonance imaging and ultrasound) were useful for visualizing the pathophysiology of lateral epicondylosis. However, the severity of the pathophysiology was not related to pain and function, indicating that imaging measures may not provide the best clinical assessment.

The effect of lateral epicondylosis on upper limb mechanical parameters.

BACKGROUND: Lateral epicondylosis is a prevalent and costly musculoskeletal disorder characterized by degeneration of the common extensor tendon origin at the lateral epicondyle. Grip strength is commonly affected due to lateral epicondylosis. However, less is known about the effect of lateral epicondylosis on other functional parameters such as ability to react to rapid loading. METHODS: Twenty-nine lateral epicondylosis participants and ten controls participated in a case-control study comparing mechanical parameters (mass, stiffness and damping), magnetic resonance imaging signal intensity and grip strength of injured and uninjured limbs. A mixed effects model was used to assess the effect of dominance and injury on mechanical parameters and grip strength. FINDINGS: Significant effect of injury and dominance was observed on stiffness, damping and grip strength. An injured upper limb had, on average, 18% less stiffness (P<0.01, 95% CI [9.8%, 26%]), 21% less damping (P<0.01, 95% CI [11%, 31%]) and 50% less grip strength (P<0.01, 95% CI [37%, 61%]) than an uninjured upper limb. The dominant limb had on average 15% more stiffness (P<0.01, 95% CI [8.0%, 23%], 33% more damping (P<0.01, 95% CI [22%, 45%]), and 24% more grip strength (P<0.01, 95% CI [6.6%, 44%]) than the non-dominant limb. INTERPRETATION: Lower mechanical parameters are indicative of a lower capacity to oppose rapidly rising forces and quantify an important aspect of upper limb function. For individuals engaged in manual or repetitive activities involving the upper limb, a reduction in ability to oppose these forces may result in increased risk for injury or recurrence.

Effect of lateral epicondylosis on grip force development.

STUDY DESIGN: Case-Control. INTRODUCTION: Although it is well known that grip strength is adversely affected by lateral epicondylosis (LE), the effect of LE on rapid grip force generation is unclear. PURPOSE OF THE STUDY: To evaluate the effect of LE on the ability to rapidly generate grip force. METHODS: Twenty-eight participants with LE (13 unilateral and 15 bilateral LE) and 13 healthy controls participated in this study. A multiaxis profile dynamometer was used to evaluate grip strength and rapid grip force generation. The ability to rapidly produce force is composed of the electromechanical delay and rate of force development. Electromechanical delay is defined as the time between the onset of electrical activity and the onset of muscle force production. The Patient-rated Tennis Elbow Evaluation (PRTEE) questionnaire was used to assess pain and functional disability. Magnetic resonance imaging was used to evaluate tendon degeneration. RESULTS: LE-injured upper extremities had lower rate of force development (50 lb/sec, confidence interval [CI]: 17, 84) and less grip strength (7.8 lb, CI: 3.3, 12.4) than nonnjured extremities. Participants in the LE group had a longer electromechanical delay (- 59% , CI: 29, 97) than controls. Peak rate of force development had a higher correlation (r = 0.56; p<0.05) with PRTEE function than grip strength (r = 0.47; p<0.05) and electromechanical delay (r = 0.30; p>0.05) for participants with LE. In addition to a reduction in grip strength, those with LE had a reduction in rate of force development and an increase in electromechanical delay. CONCLUSIONS: Collectively, these changes may contribute to an increase in reaction time, which may affect risk for recurrent symptoms. These findings suggest that therapists may need to address both strength and rapid force development deficits in patients with LE. LEVEL OF EVIDENCE: 3B.

Musculoskeletal applications of platelet-rich plasma: fad or future?

OBJECTIVE: The purpose of this article is to detail the biology of platelet-rich plasma (PRP), critically review the existing literature, and discuss future research applications needed to adopt PRP as a mainstay treatment method for common musculoskeletal injuries. CONCLUSION: Any promising minimally invasive therapy such as PRP deserves further investigation to avoid surgery. Diagnostic imaging outcome assessments, including ultrasound-guided needle precision, should be included in future investigations.

The efficacy of prolotherapy for lateral epicondylosis: a pilot study.

OBJECTIVES: To assess whether prolotherapy, an injection-based therapy, improves elbow pain, grip strength, and extension strength in patients with lateral epicondylosis. SETTING: Outpatient Sport Medicine clinic. STUDY DESIGN: Double-blind randomized controlled trial. PARTICIPANTS: Twenty-four adults with at least 6 months of refractory lateral epicondylosis. INTERVENTION: Prolotherapy participants received injections of a solution made from 1 part 5% sodium morrhuate, 1.5 parts 50% dextrose, 0.5 parts 4% lidocaine, 0.5 parts 0.5% sensorcaine and 3.5 parts normal saline. Controls received injections of 0.9% saline. Three 0.5-mL injections were made at the supracondylar ridge, lateral epicondyle, and annular ligament at baseline and at 4 and 8 weeks. OUTCOME MEASURES: The primary outcome was resting elbow pain (0 to 10 Likert scale). Secondary outcomes were extension and grip strength. Each was performed at baseline and at 8 and 16 weeks. One-year follow-up included pain assessment and effect of pain on activities of daily living. RESULTS: : The groups were similar at baseline. Compared to Controls, Prolotherapy subjects reported improved pain scores (4.5 +/- 1.7, 3.6 +/- 1.2, and 3.5 +/- 1.5 versus 5.1 +/- 0.8, 3.3 +/- 0.9, and 0.5 +/- 0.4 at baseline and at 8 and 16 weeks, respectively). At 16 weeks, these differences were significant compared to baseline scores within and among groups (P < 0.001). Prolotherapy subjects also reported improved extension strength compared to Controls (P < 0.01) and improved grip strength compared to baseline (P < 0.05). Clinical improvement in Prolotherapy group subjects was maintained at 52 weeks. There were no adverse events. CONCLUSIONS: Prolotherapy with dextrose and sodium morrhuate was well tolerated, effectively decreased elbow pain, and improved strength testing in subjects with refractory lateral epicondylosis compared to Control group injections.

Response of knee ligaments to prolotherapy in a rat injury model.

BACKGROUND: Prolotherapy is an alternative therapy for chronic musculoskeletal injury including joint laxity. The commonly used injectant, D-glucose (dextrose), is hypothesized to improve ligament mechanics and decrease pain through an inflammatory mechanism. No study has investigated the mechanical effects of prolotherapy on stretch-injured ligaments. HYPOTHESES: Dextrose injections will enlarge cross-sectional area, decrease laxity, strengthen, and stiffen stretch-injured medial collateral ligaments (MCLs) compared with controls. Dextrose prolotherapy will increase collagen fibril diameter and density of stretch-injured MCLs. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-four rats were bilaterally MCL stretch-injured, and the induced laxity was measured. After 2 weeks, 32 MCLs were injected twice, 1 week apart, with either dextrose or saline control; 16 MCLs received no injection. Seven uninjured rats (14 MCLs) were additional controls. Two weeks after the second injection, ligament laxity, mechanical properties (n = 8), and collagen fibril diameter and density (n = 3) were assessed. RESULTS: The injury model created consistent ligament laxity (P < .05) that was not altered by dextrose injections. Cross-sectional area of dextrose-injected MCLs was increased 30% and 90% compared with saline and uninjured controls, respectively (P < .05). Collagen fibril diameter and density were decreased in injured ligaments compared with uninjured controls (P < .05), but collagen fibril characteristics were not different between injured groups. CONCLUSION: Dextrose injections increased the cross-sectional area of MCLs compared with saline-injected and uninjured controls. Dextrose injections did not alter other measured properties in this model. CLINICAL RELEVANCE: Our results suggest that clinical improvement from prolotherapy may not result from direct effects on ligament biomechanics.

Early inflammatory response of knee ligaments to prolotherapy in a rat model.

Prolotherapy is an alternative injection-based therapy for chronic musculoskeletal pain. Three different proliferants, D-glucose (dextrose), phenol-glucose-glycerine (P2G), and sodium morrhuate, used in prolotherapy are hypothesized to strengthen and reorganize chronically injured soft tissue and decrease pain through modulation of the inflammatory process. Our hypothesis is that commonly used prolotherapy solutions will induce inflammation (leukocyte and macrophage infiltration) in medial collateral ligaments (MCLs) compared to needlestick, saline injection, and no-injection controls. MCLs of 84 Sprague- Dawley rats were injected one time at both the tibial and femoral insertions. Immunohistochemistry (IHC) was used to determine the inflammatory response at three locations (tibial and femoral insertions and midsubstance) 6, 24, and 72 h after dextrose injection compared to saline- and no-injection controls and collagenase (positive control) (n = 4). qPCR was used to analyze gene expression 24 h postinjection (n = 4). Sodium morrhuate, P2G, and needlestick control were also investigated after 24 h (n = 4). In general, inflammation (CD43+, ED1+, and ED2+ cells) increased after prolotherapy injection compared to no-injection control but did not increase consistently compared to saline and needlestick control injections. This response varied by both location and proliferant. Inflammation was observed at 6 and 24 h postinjection but was resolved by 72 h compared to no-injection controls (p < 0.05). CD43+ leukocytes and ED2+ macrophages increased compared to needlestick and saline-injection control, respectively, 24 h postinjection (p < 0.05). Prolotherapy injections created an inflammatory response, but this response was variable and overall, not uniformly different from that caused by saline injections or needlestick procedures.

CAM therapies among primary care patients using opioid therapy for chronic pain.

BACKGROUND: Complementary and alternative medicine (CAM) is an increasingly common therapy used to treat chronic pain syndromes. However; there is limited information on the utilization and efficacy of CAM therapy in primary care patients receiving long-term opioid therapy. METHOD: A survey of CAM therapy was conducted with a systematic sample of 908 primary care patients receiving opioids as a primary treatment method for chronic pain. Subjects completed a questionnaire designed to assess utilization, efficacy and costs of CAM therapies in this population. RESULTS: Patients were treated for a variety of pain problems including low back pain (38.4%), headaches (9.9%), and knee pain (6.5%); the average duration of pain was 16 years. The median morphine equivalent opioid dose was 41 mg/day, and the mean dose was 92 mg/day. Forty-four percent of the sample reported CAM therapy use in the past 12 months. Therapies utilized included massage therapy (27.3%, n = 248), chiropractic treatment (17.8%, n = 162), acupuncture (7.6%, n = 69), yoga (6.1%, n = 55), herbs and supplements (6.8%, n = 62), and prolotherapy (5.9%, n = 54). CAM utilization was significantly related to age female gender, pain severity income pain diagnosis of neck and upper back pain, and illicit drug use. Medical insurance covered chiropractic treatment (81.8%) and prolotherapy (87.7%), whereas patients primarily paid for other CAM therapies. Over half the sample reported that one or more of the CAM therapies were helpful. CONCLUSION: This study suggests CAM therapy is widely used by patients receiving opioids for chronic pain. Whether opioids can be reduced by introducing such therapies remains to be studied.